Search

At our hospital, anti-cancer drug administration is managed using a regimen-ordering system, and orders for the outpatient department and hospital wards have to be placed by 15:00 and 14:00 the day before they are required. On the day of treatment, the doctor examines the patient, confirms the test results, and places the final order for treatment on the patient's electronic medical record. In response, the pharmacist adjusts the anti-cancer drug preparation, and treatment is provided in the outpatient setting or in a ward. Although drug costs have increased due to the widespread use of immunotherapy, there have been cases where a drug was wasted after the required amount was adjusted on the day of treatment or drugs were discarded altogether, which pose serious problems. From April 2016 to March 2021, the total number of cases of drug wastage following placement of the final treatment order and drug disposal were 146 and 84, respectively, and the total associated economic loss was 5.81 million yen. The main causes were pre-confirmation mistakes and patients' physical condition on the day of treatment; some cancellations caused by patient-related factors were unavoidable. The current status of drug disposal is reported to the hospital director every 6 months, and the doctor-in-charge is interviewed regarding the reason for the wastage. In cases involving the disposal of large quantities of drugs(≥100,000 yen), the department manager and medical office manager are contacted, and an incident report is submitted. In 2021, drugs worth 2.03 million yen were discarded between April and September, which is worth serious consideration. It is essential to understand the reasons for drug wastage, pay attention to expensive regimens, and take appropriate measures at each facility.

We conducted a survey of the outpatient pharmacotherapy we administered from April 2016 to March 2019 to understand trends in chemotherapy for respiratory thoracic malignancies, such as lung cancer. Over the 3-year period, 19,408 were treated in the outpatient chemotherapy department. Of these, 1,270(6.5%)had respiratory thoracic malignancies. The total number of patients and the number of patients with thoracic malignancies(%) were 5,815 and 320(5.5%); 6,344 and 434(6.8%); and 7,247 and 516(7.1%)in FY2016, FY2017 and FY2018, respectively. This shows that both increased during the study period. Each patient was treated in the chemotherapy department multiple times, and treatment for thoracic malignancies was initiated in 161 patients. The female:male ratio was 27%:73%, and the patients' median age(range)was 68 years(range: 36-84 years). Lung cancer was the most common disease(91%), followed by malignant pleural mesothelioma(5%), thymoma(2%), thymic carcinoma(1%), and synovial sarcoma(1%). The most common histological type of lung cancer was adenocarcinoma(67%), followed by squamous cell carcinoma(17%), small cell carcinoma( 7%), and others(9%). Outpatient chemotherapy was introduced as a first-line, second-line, and third-line or later treatment in 46%, 28%, and 22% of cases, respectively. While the number of patients increased, the number of new patients with thoracic malignancies decreased from 58 in FY2016 to 52 in FY2017 and 51 in FY2018. Conversely, the number of visits to the chemotherapy department by each new patient almost doubled from 5.5 in FY2016 to 8.5 in FY2017 and 10.1 in FY2018. The proportion of patients for which immunotherapy was included in the induction treatment regimen increased from 28% and 24% in FY2016 and FY2017, respectively, to 39% in FY2018. The increase in the use of outpatient chemotherapy for respiratory thoracic malignancies was due to the increase in the proportion of patients undergoing immunotherapy and the number of visits to the chemotherapy department per patient. It is important to implement measures to help prolong and increase the use of outpatient pharmacotherapy for respiratory thoracic malignancies by cooperating with surrounding medical institutions and increasing the number of beds available.

Nitric oxide (NO), formed from NO synthases (NOSs), plays a pathogenetic role in pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains to be clarified. We addressed this point in clinical and basic studies. We demonstrated that, in 36 consecutive patients with idiopathic pulmonary fibrosis, pulmonary artery systolic pressure is inversely correlated with NOx levels in the bronchoalveolar lavage fluid, suggesting reduced pulmonary NO production in group III PH. We then revealed that transplantation of BM cells from mice lacking all NOSs aggravates hypoxia-induced PH in wild-type (WT) mice, and transplantation of BM cells from the WT mice ameliorates hypoxia-induced PH in the NOSs -/- mice, indicating a protective role of myelocytic NOSs in the pathogenesis of PH. Immune and inflammatory mechanisms appeared to be involved in the aggravation of hypoxia-induced PH caused by transplantation of BM cells from the NOSs -/- mice. Our findings provide novel insights into the cellular and molecular basis of group III PH.

The number of patients with pneumonia has been increasing as the population ages, and most fatal pneumonia cases are the elderly with aspiration pneumonia. Although aspiration pneumonia leads to poor short- and long-term prognosis, there have been no practical ways to diagnose it precisely. Persistent subclinical aspiration without any subjective symptoms is problematic in clinical practice in patients with aspiration pneumonia, and physicians can only use aspiration risks such as brain infarction to diagnose aspiration pneumonia. Anaerobes have been believed to be major causative pathogens in aspiration pneumonia, based on data from the 1970's. In relation to these data, Marik insisted that there is a possible overestimation of anaerobes because 1) the sampling of microbiologic specimens was in the late phase in the course of the illness, especially frequently after developing complications such as abscesses, necrotizing pneumonia, or empyema thoracis; 2) the organisms recovered by percutaneous transtracheal aspiration (PTA) sampling could have been contaminated by the aspiration of oropharyngeal flora during the PTA procedure or colonized in the trachea; and 3) many of the patients had chronic alcoholism or were under general anesthesia. In addition, 4) oral care was not common in the 1970s, and 5) the patients in these reports were relatively young. Molecular biological approaches using the 16S ribosomal RNA (rRNA) gene have recently been used, and have enabled us to detect more exact pathogens compared to conventional bacterial culture. Using the method with the detection of the 16S rRNA gene, we evaluated the bacterial phylotypes in bronchoalveolar lavage fluid in patients with aspiration pneumonia and found that oral streptococci were the most detected phylotypes (31.0%), while anaerobes were only 6.0%. Our results suggest that oral streptococci are important, and anaerobes may have been overestimated as causative pathogens in patients with aspiration pneumonia.

An eighty-nine-year-old Japanese male was admitted to our hospital due to dry cough and dyspnea. Respiratory symptoms appeared soon after an administration of an oriental medicine, Kamikihito for tinnitus. Upon admission, chest computed tomography showed patchy consolidations and ground-glass opacities in the right upper lobe of the lungs, and ground-glass opacities in the bilateral lower lobes. Sulbactam-ampicillin combination (SBT/ABPC, 3 g × 2/day) was started in addition to the change or cessation of several other drugs, including Kamikihito, resulting in respiratory symptoms and chest radiographic exacerbations. Bronchoalveolar lavage fluid obtained from the right S 3 showed an increase in the total cell number of lymphocytes. A drug lymphocyte stimulation test (DLST) for Kamikihito was also positive. Kamikihito-induced lung injury was most likely, and treatment with prednisolone (50 mg/day) was started. His respiratory symptoms and chest radiographic findings improved rapidly soon after initiating oral prednisolone. This is the first report of Kamikihito-induced lung injury.

Ectopic soft tissue calcification (ESTC), a rare clinical condition, causes tissue and organ damage. It is associated with chronic renal failure, hyperparathyroidism, and malignant neoplasms, including multiple myeloma, and it is reportedly resistant to treatment. Here, we present the case of a 71-year-old male with multiple myeloma who had rapid ESTC in the lung. He had developed hypoparathyroidism secondary to thyroidectomy. During the course of our observation, he rapidly developed ectopic pulmonary calcification approximately 2 weeks after acquiring an infection. There was no evidence of further progression of multiple myeloma after the onset of ESTC, and treatment with ferric citrate hydrate and precipitated calcium resulted in immediate improvement of his pulmonary signs. We recommend cautious monitoring for patients with multiple myeloma and hypoparathyroidism to detect the onset of ectopic calcification. In addition, low blood phosphorus levels should be effectively treated.

Objective: A retrospective analysis on carboplatin(CBDCA)/nanoparticle albumin-boundpaclitaxel(nab-PTX)combination chemotherapy was conducted in patients with non-small-cell lung cancer(NSCLC)to evaluate both the efficacy and toxicity based on age, treatment line, histology, and underlying diseases., Subjects: A total of 27 patients with advanced or recurrent NSCLC following surgery who receivedCBDCA /nab-PTX as first- andsecond -line combination chemotherapy, respectively, were investigatedfrom March 2013 to December 2015., Results: The overall response rate, median progressionfree survival, andmed ian overall survival of all patients were 37.0%, 5.5 months, and 11.4 months, respectively. With regard to toxicity, 3.7%and 14.8%of all patients had peripheral disorder and interstitial lung disease(ILD), respectively. Treatmentrelatedd eaths were not observed. No difference in the efficacy basedon age, treatment line, histology, andund erlying diseases was observed., Conclusion: CBDCA/nab-PTX combination chemotherapy was safe for elderly patients and those with ILD. However, the occurrence of new interstitial lung lesions should be carefully considered.

A 50-year-old female with a history of chronic sinusitis and rheumatoid arthritis visited our department with repetitive lower respiratory tract infections of Pseudomonas aeruginosa. Her chest CT showed diffuse panbronchiolitis-like pulmonary lesions, her blood examination revealed atypical lymphocytes, and she was serologically positive for anti-human T-lymphotrophic virus type 1 (HTLV-1) antibody. Her rheumatoid arthritis had been well-controlled after biological agent treatment followed by anti-inflammatory analgesic treatment. She received long-term low-dose macrolide therapy for four years. The Pseudomonas aeruginosa gradually became multi-antibiotic-resistant. Her lower respiratory infection gradually became uncontrollable, and her adult T cell leukemia (ATL) developed to the acute phase. Due to repetitive lower respiratory tract infections and respiratory failure, however, she could not receive any treatment for ATL, and she eventually died due to the progression of the disease. An autopsy revealed an invasion of abnormal lymphocytes in multiple organs, including the lungs, which indicated that the HTLV-1 infection and the progression of ATL were the dominant factors in this patient's clinical course. There have been no diffuse panbronchiolitis-like cases accompanied by rheumatoid arthritis and HTLV-1 infection so far. Because these diseases show similar clinical features, it is difficult to discriminate between them. There are presently no appropriate criteria for the proper time of treatment of patients with pulmonary lesion-associated ATL, but further research is expected to elucidate this matter.

A 42-year-old woman was referred to our hospital with a diagnosis of influenza A and pneumonia out of the influenza season. Chest CT findings resembled interstitial pneumonia, but we initiated anti viral agents and antibiotics. Flexible fiberoptic bronchoscopy was performed on hospital day 3. Based on the results of an RT-PCR analysis of broncho-alveolar lavage, this patient was diagnosed as having influenza viral pneumonia. In the influenza season, we can easily suspect influenza as a differential diagnosis, even if the patient's chest CT findings resemble interstitial pneumonia. Out of the influenza season, clinicians should take into consideration influenza viral pneumonia as a differential diagnosis.

The balance of "Host-Pathogen-Antimicrobials" is crucial for the establishment of infectious diseases. Recently the ineffective cases, even though the appropriate antibiotics use, have been increasing since the several ineludible problems are rising, such as varied patient's background and the epidemic of the drug resistant pathogens, etc. Despite of the medical progression and the development of novel antimicrobials, the mortality of pneumonia has increased gradually and been the third cause of death in Japan. The conventional treatment depended on only bactericidal effect of antimicrobials faces a limit and the alternative strategies are required to overcome the current situation. This review addresses the potency of non-antibiotic antimicrobial agents as an alternative therapeutic strategy, especially focused on the activation of the innate host immunity induced by the macrolides and toll-like receptor agonist.

Endobronchial ultrasonography with a guide sheath (EBUS-GS) has recently been used for improved diagnostic yields for peripheral pulmonary lesions. This study retrospectively evaluated the factors related to the diagnostic yield of EBUS-GS for peripheral lung cancer. The medical records of 76 patients who had been diagnosed with lung cancer and had undergone bronchoscopy with EBUS-GS in our hospital between August 2014 and September 2015 were reviewed. The total diagnostic ratio of peripheral lung cancer was 71.1%. The following factors of the diagnostic yield were evaluated: location of pulmonary lesion; size; feature; bronchus sign; location of EBUS probe; EBUS detection; number of biopsies performed; procedure time; use of virtual bronchoscopic navigation; use of EBUS-guided transbronchial needle aspiration with EBUS-GS; CT slice thickness; operator's years of medical experience; and specialized training in bronchoscopy at the National Cancer Center. In all cases, lesion size ≧ 20 mm (80.8% vs. 50.0%, P = 0.006), EBUS probe location "within" (90.0% vs. 50.0%, P < 0.001), EBUS detection (80.7% vs. 28.6%, P < 0.001), number of biopsies ≧ 5 (78.0% vs. 47.1%, P = 0.013), and bronchoscopy training (81.6% vs. 60.5%, P = 0.043) significantly contributed to an increase in the diagnostic yield. Following a multivariate analysis, EBUS probe location "within" was found to be the most significant factor affecting the diagnostic yield (odds ratio 14.10, 95% CI 3.53-56.60, P < 0.001), and bronchoscopy training was the second most significant factor (odds ratio 6.93, 95% CI 1.86-25.80, P = 0.004). EBUS probe location "within" and bronchoscopy training are the most important factors for improved diagnostic yield by bronchoscopy with EBUS-GS for peripheral lung cancer.

Helicobacter cinaedi is typically isolated from immunocompromised patients. Some reports of infection caused by H.cinaedi have been found in recent years. We experienced three cases of H.cinaedi bacteremia in one year and ten months in our hospital, although the detection of H.cinaedi in blood cultures is extremely rare. In case 1, a 77-year-old female had been treated with a steroid and immunosuppressive agent for interstitial pneumonia. In cases 2 and 3, two 71-year-old men had been treated with chemotherapy for lung cancer. Although the identification of the bacteria could not be performed by the culture method in the three cases, H.cinaedi bacteremia was diagnosed by a 16S rRNA gene sequencing analysis in case 1, and by nested PCR in cases 2 and 3. H.cinaedi bacteremia often tends to recur and also requires prolonged antimicrobial therapy. We believe that gene analysis is useful in the identification of H.cinaedi.

A 73-year-old Japanese man visited a local hospital due to palpitations and dyspnea. He was diagnosed as having lung cancer (adenocarcinoma, cT1aN2M1b (BRA), stage Ⅳ), but he did not want to receive any anticancer medications, and was simply being observed. Several months later, he was referred to our hospital due to exacerbation of the dyspnea. His chest computed tomography revealed massive pericardial effusion, therefore he was diagnosed as having cardiac tamponade due to carcinomatous pericarditis and was immediately hospitalized. Upon admission, pericardial fenestration was firstly applied in order to drain pericardial effusion, and intraoperative cardiac findings showed suspicion of myocardial and pericardial metastasis. Immediately after the pericardiotomy, he suffered from cardiac arrest caused by shock. In lung cancer patients with pericardial effusion, even though it is rare, myocardial metastasis in addition to carcinomatous pericarditis and pericardial metastasis should be kept in mind.

Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

A 25-year-old Chinese man with no medical history of pulmonary tuberculosis visited to a hospital for an evaluation of chest X-ray abnormal findings of routine health checkup. Chest computed tomography (CT) demonstrated chest wall mass surrounded by calcified walls in the right anterior chest wall. Eighteen months later, he found subcutaneous mass lesion in the right hypochondriac lesion, and this mass became painful in 5 days. Therefore he visited our hospital, and his chest CT showed low density mass with thickened calcified walls in the right anterior thoracic space, small amount of right pleural effusion and subcutaneous localized mass. A needle aspiration of the right subcutaneous mass demonstrated that the specimen were all negative for acid-fast bacilli smear, culture and PCR for M. tuberculosis. On the contrary, right pleural effusion showed positive for PCR for M. tuberculosis, in spite of negative results of acid-fast bacilli smear and culture. Pericostal tuberculosis that was progressed by the rupture of old calcified tuberculous empyema in the chest wall was confirmed. Antituberculous chemotherapy, chest tube drainage for right subcutaneous mass and pleural decortication and empyema were successfully performed. Pericostal tuberculosis should be differentially considered when the calcified mass in the chest wall changes its shape.

Two cases of acute respiratory distress syndrome related to zinc fume inhalation and zinc powder inhalation are presented. Case 1 demonstrated acute respiratory symptoms during the work of distortion correction of iron boards, coated with a rust preventative including rich zinc using an acetylene gas burner. Case 2 occurred after the work of applying a rust preventative that included zinc powder, mainly using an airless compressor. Since both were working in a boathouse, without using protective equipment, the possible causes of Case 1 and 2 were inhalation exposure to zinc fumes and zinc powder, respectively. The two patients showed similar clinical courses, including favorable treatment outcomes, mimicking acute respiratory failure complicated by a metal fume fever.

In the present study, we evaluated the antiemetic effect of aprepitant in combination with 5-hydroxytryptophan(5-HT3) receptor antagonist and dexamethasone for chemotherapy-induced emesis and nausea in lung cancer patients treated with carboplatin-based systemic chemotherapy using the Functional Living Index-Emesis, an emesis- and nausea-specific quality of life(QOL)questionnaire. Patients experiencing emesis and/or nausea during and/or after previous courses of carboplatin-based chemotherapy received aprepitant in the following treatment cycle with the same anti-cancer agent. Emesis- and nausea-specific QOL aspects were significantly improved with the addition of aprepitant to the existing regimen containing dexamethasone and 5-HT3 receptor antagonist. Our result suggests that combined antiemetic treatment with aprepitant, dexamethasone, and 5-HT3 receptor antagonist is more effective in lung cancer patients receiving carboplatin-based systemic chemotherapy than dexamethasone and 5-HT3 receptor antagonist alone.

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

Moxifloxacin (MFLX) is a respiratory quinolone, and is effective against not only Gram-positive and negative bacteria but also anaerobes. There has been no prospective studies evaluating the efficacy and safety of MFLX in patients with nursing and healthcare-associated pneumonia (NHCAP). Therefore, we assessed the efficacy and safety of MFLX in patients with NHCAP. NHCAP patients with mild and moderate severity assessed by the A-DROP system in community-acquired pneumonia guideline proposed by Japan Respiratory Society visited our hospitals from April 2011 to March 2012. Clinical symptoms, chest X-ray films and/or computed tomography, peripheral white and red blood cell and platelet counts, serum CRP, AST, ALT, BUN, creatinine were evaluated. Forty patients were eventually evaluated, and average age was 74.1 years old, male/female were 21/19, 92.5% (37/40) of them had one or more comorbidities. Median duration of MFLX administration was 7.1 days (4-15 days). The efficacy of MFLX in all patients was 87.5% (35/40). The efficacies in each age group were 87.9% (aged over 65 years old), 85.7% (aged under 64 years old), and in each pneumonia severity group by the A-DROP system were 91.7% (mild), 85.7% (moderate). Diarrhea and swelling of the breast were observed in one patient (2.5%) after starting MFLX administration. Mild elevated transaminases were observed in three patients (7.5%), and mild renal dysfunction was observed in two patients (5.0%). All abnormally increased levels of transaminases and serum creatinine were recovered after a cessation of MFLX. MFLX is effective and safe in patients with NHCAP.

A 54 year old Japanese man was introduced to Saiseikai General hospital for an evaluation of an abnormal chest X-ray film. Abnormal soft tissue area was observed in the mediastinum surrounding anterior area of the trachea on chest CT. Because the mediastinal tumor showed slow enlargement after temporal decrease and surgical resection of the tumor was performed 3 years after the first visit. Pathologically, diffuse proliferation of oval-shaped plasmacytic or small lymphocytic cells with eccentrically-located nuclei with rough chromatin were observed in the tumor. Immunohistochemically, these cells were positive for CD20, weakly positive for IgM, negative for CD3, CD5, CD10, suggesting lymphoplasmacytic lymphoma (LPL). The patient was treated with rituximab after the surgical treatment, and showed no exacerbation for 3.5 years after surgery. LPL localized to the paratracheal mediastinum is rare, and a surgical approach is important for prompt and proper diagnosis.

An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis.

We have retrospectively analyzed the safety of 4 hours administration of liposomal amphotericin B (L-AMB) compared to less than or equal to 3 hours administration in patients with chronic necrotizing pulmonary aspergillosis (CNPA). The elevation of serum creatinine in the group with 4 hours administration of L-AMB in patients with CNPA was equal to the group with shorter administration time (less than or equal to three hours). During the administration of L-AMB, the group with 4 hours administration of LAMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment than the group with shorter administration time. Additionally, white cell counts, platelet counts, serum creatinine, AST, ALT were not significantly different between L-AMB 4 hours administration group and less than or equal to 3 hours administration group. As the group with 4 hours administration of L-AMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment, this modality can be one of the safer ways in the treatment of CNPA. As L-AMB is one of the fungicidal agents, 4 hours administration of L-AMB can be an optimal way of treating CNPA.

An 80-year-old Japanese male was admitted to our hospital because of bloody sputum. He had a history of malignant melanoma of the left fourth digit, which was surgically excised 16 years previously. On hospital admission, chest computed tomography revealed several nodules in the lower lobes. He underwent thoracoscopic lung biopsy and amelanotic malignant melanoma was histologically diagnosed by immunohistochemical staining. The staining pattern with several antibodies was similar to that of the melanoma excised 16 years previously. Therefore, we concluded that the nodules in the lung were metastases of the malignant melanoma of the digit. Despite treatment with interferon, the nodules progressed rapidly, and the patient died 4 months later. This case suggests that the risk of recurrence with rapidly progressive distant metastasis should be considered in patients with malignant melanoma, even after a long disease-free interval. In addition, this case suggests that immunohistochemical stains with several antibodies are useful in the diagnosis of malignant melanoma.

We investigated the efficacy and safety of sitafloxacin (STFX) in patients with mild to moderate community-acquired pneumonia or secondary infections of chronic respiratory tract diseases. The results showed that the efficacy rate was 96.5% (111/115) in patients analyzed for efficacy. The efficacy rate by STFX administration method was 93.9% (46/49) at 50mg b.i.d., 100% (37/37) at 100 mg q.d. and 96.6% (28/29) at 100mg b.i.d. In chest X-rays, the image improvement rate in 102 patients with shadows before treatment was 94.1% (96/102). The image improvement rate by STFX administration method was 90.5% (38/42) at 50 mg b.i.d., 97.1% (33/34) at 100mg q.d. and 96.2% (25/26) at 100mg b.i.d. Side effects occurred in five out of 115 patients (4.3%). Abnormalities in hepatic function test values appeared in two patients and abnormalities in renal function test values appeared in three patients. In four cases, the abnormalities were very mild and STFX administration was continued without any treatment. In the other patient, the abnormal value rapidly returned to normal after STFX administration was discontinued. These findings indicated that STFX can be used safety in routine practice by adjusting the administration within the approved dose based on patient characteristics. Good therapeutic effects can be expected in patients with respiratory tract infections.

A 78 year old Japanese woman was transferred to our hospital for the treatment of a fracture of the left femoral neck in April, 2010. She had been taking oral corticosteroid (prednisolone 5 mg/day) for the treatment of idiopathic interstitial pneumonia since 2003, and had been treated by home oxygen therapy since 2007. She fell in the restroom at home and hurt herself, and was transferred to our hospital for treatment of a left femoral neck fracture in April, 2010. Her respiratory status was stable just after the transfer; however, she was transferred to the intensive care unit and started to receive mechanical ventilation due to rapidly progressive respiratory failure on the fourth day after admission. Chest X-ray and computed tomography revealed rapid progression of bilateral ground-glass attenuations, and acute exacerbation of interstitial pneumonia was clinically suspected. However, the elevation of D-dimer over time and characteristic findings of petechial hemorrhagic lesions on her palpebral conjunctivae and neck with microscopic findings of phagocytized lipid in alveolar macrophages in her endobronchial secretion led to the diagnosis of fat embolism syndrome. She was successfully treated with high-dose corticosteroid and sivelestat sodium, and she was discharged on the 21st day after admission. Although a differential diagnosis of acute exacerbation of interstitial pneumonia and fat embolism syndrome was necessary and difficult in the present case, characteristic findings of petechial hemorrhagic lesions of skin, palpebral conjunctiva and lipid-laden alveolar macrophages in endotracheal aspirate were useful for the accurate and prompt diagnosis of fat embolism syndrome.

A 42-year-old Japanese woman was referred to our university hospital due to progressive anemia and bilateral hilar lymphadenopathy with diffuse ground-glass attenuation on chest computed tomography in December 2009. She had suffered from exertional dyspnea and fatigue for several months. Laboratory findings on admission demonstrated leukocytosis (10,950/ul), elevation of C-reactive protein (4.7 mg/dl), IL-6 (19.9 pg/ml), IgG4 (567 mg/dl) and polyclonal hyper gamma-globulinemia. Chest computed tomography represented mediastinal and bilateral hilar lymphadenopathy with diffuse centrilobular fine nodules and intralobular septal thickening. Histopathological findings of the specimens obtained by thoracoscopic lung and mediastinal lymph node biopsies revealed massive infiltration of IgG4-positive plasma cells in lung tissue and lymph nodes. Pathological findings and high levels of C-reactive protein and interleukin-6 suggested a diagnosis of multicentric Castleman's disease (MCD). In addition, pathological findings of peribronchiolar infiltration of IgG4-positive plasma cells and lymphoid follicles with infiltration of IgG4-positive plasma cells with a high level of IgG4 were indicative of the complication of IgG4-related lung disease. Radiological and serological findings improved rapidly soon after the initiation of oral corticosteroid treatment. It was speculated that this case indicated the close relationship between MCD and IgG4-related lung disease.

A 74-year-old man was referred to our hospital for examination of an abnormal chest shadow. A chest computed tomography (CT) scan revealed a 5-cm mass attached to the pleura involving the right upper lobe, and a nodule in the right middle lobe. Transbronchial lung biopsy was performed twice, but no definitive diagnosis was achieved. 18-fluorodeoxyglucose positron emission tomography showed abnormal uptake in the chest lesion. Chemotherapy was initiated for advanced-stage lung cancer, but was not effective. Histopathologic and immunohistochemical examinations after CT-guided needle biopsy revealed malignant mesothelioma. The tumor cells were positive for calretinin and thrombomodulin, and negative for CEA, TTF-1, and SP-A. There was local tumor invasion and metastasis in the lung and brain, without diffuse pleural spread. This is a rare and important case of localized malignant mesothelioma pathologically confirmed by biopsy.

A 36-year-old woman was admitted to the obstetric department because of possible premature labor of twins at 35 weeks. She had been treated by ritodrine hydrochloride, a tocolytic agent, for 1 week, and delivered healthy twins by cesarean operation. After the operation, she suddenly complained of dyspnea with associated hypoxemia and was admitted to our hospital. She presented with hypoxemia and was given a diagnosis of pulmonary edema. She was given a diuretic with ventilator therapy, and improved rapidly. However, an echocardiogram showed continuing left ventricular systolic dysfunction after 3 months. From these results, this case was suspected to be pulmonary edema due to ritodrin after myocardial failure, including peripartum cardiomyopathy.

A 75-year-old man, who had eaten wild boar and deer repeatedly until November 2006, visited our hospital because of a right pleural effusion on chest X-ray films after he bruised a hip in January 2007. A right thoracocentesis revealed exudative pleural effusion with many neutrophils. Ten days after his first visit, a pleural biopsy specimen suggested the existence of parasite eggs. Twenty-six days after his first visit, he was admitted to our hospital because of leukocytosis, increased systemic inflammatory markers and a right pleural effusion. We found a great number of neutrophils, eggs of the Paragonimus species and gram-positive cocci in the pleural effusion. Streptococcus pneumoniae was also identified in his pleural effusion. In addition, a diagnosis of Paragonimiasis westermani was made serological study. After the continuous drainage of the pleural effusion, the patient was treated with praziquantel and antibiotics, and he gradually improved.

We reported 3 cases of hypersensitivity pneumonitis who had been exposed to polyurethane material containing diphenylmethane diisocyanate (MDI) for 1-12 weeks. They had cough, fever and dyspnea before admission. All 3 cases were diagnosed immunologically using anti-MDI antibodies. Chest HRCT findings of the 3 cases were different. Case 1 showed an organizing pneumonia (OP) pattern : patchy peripheral consolidation with air bronchogram and ground-glass opacities (GGO), and case 2 showed a nonspecific interstitial pneumonia (NSIP) pattern : consolidation and reticular shadows in both lower lobes. In addition, case 3 showed a hypersensitivity pneumonitis (HP) pattern : centrilobular GGO and diffuse granular shadows. All cases were successfully treated by corticosteroids alone. This suggests that different amounts of inhaled antigen can cause different HRCT findings.

We report two cases of pleomorphic carcinoma with fever and severe inflammatory reaction. In case 1, an abnormal mass shadow was found on the chest X-ray film of a 63-year-old man with bloody sputum. After right upper lobectomy, the tumor was diagnosed as pleomorphic carcinoma. About 7 months after surgical operation, he had fever and chest pain. Although his test results showed leukocytosis and his elevated serum CRP level indicated some infection, there were no signs of bacterial or fungal infection. Further examination revealed metases of lung cancer in the left adrenal gland, mediastinal and iliac lymph nodes. Serological study revealed elevated level of G-CSF, likely due to G-CSF producing metastatic tumors. In case 2, a 77-year-old man presented with continuous high fever. Examinations revealed elevated serum CRP level and multiple nodular shadows and enlarged supraclavicular and mediastinal lymph nodes on the chest CT, suggesting some infectious, connective tissue, or lymphoproliferative diseases. He was finally found to have pleomorphic carcinoma of the lung by histological examination of lymph nodes. The continuous high fever seemed to be a tumor-related fever, because it rapidly disappeared after administration of naproxen.

A 65-year-old man had been admitted with exertional dyspnea 2 years previously. Reticular shadows in bilateral lower lung fields were detected on chest roentogenogram and observed the natural course. The clinical symptoms and radiological findings progressed one month later and then he was admitted to our hospital to be examined for diagnosis and treatment. Video-assisted thoracoscopic surgery (VATS) was performed and chronic hypersensitivity pneumonitis was diagnosed. At five days after the surgery, dyspnea and radiological findings deteriorated and we diagnosed acute exacerbation of chronic hypersensitivity pneumonitis. He was treated immediately with steroid pulse therapy, immunosuppressant and polymyxin B-immobilized fiber column-direct hemoperfusion, which relieved his clinical symptoms and radiological findings. Although this is a very rare case, we have to consider the possibility of acute exacerbation of chronic hypersensitivity pneumonitis after VATS, as we do in idiopathic pulmonary fibrosis.

Objective: Neutrophil elastase is believed to play an important role in acute lung injury (ALI). Sivelestat is a small molecular weight neutrophil elastase inhibitor. Although some authors reported its efficacy in ALI, it is unclear whether sivelestat has good effects in ALI, especially in cases due to severe bacterial pneumonia. The purpose of this study is to investigate the effect of sivelestat to ALI due to severe bacterial pneumonia., Methods: We performed a retrospective study of 28 patients who were admitted for severe bacterial pneumonia (pneumonia severity index; PSI class V). We investigated the patients' background, pneumonia severity score, the days from diagnosis of systemic inflammatory response syndrome (SIRS) to sivelestat administration, P/F ratio, SIRS score, and compared two groups: those who survived and those who died., Results: There were no significant background differences between the two groups. In pneumonia severity score, chest X-ray film score was higher in the group of fatalities than in the survival group. In the survival cases, sivelestat had been administered earlier than in the cases that died. In the survival cases, improvement in P/F ratio, body temperature, heart rate, and respiratory rate were shown. The total number of SIRS scores also decreased in survival cases., Conclusion: This study suggested the possibility that early administration of sivelestat may improve the ALI survival rate in severe pneumonia.

A 32-year-old woman was admitted to our hospital because of fever and back pain. Two months previously, she had been given a diagnosis of bacterial pneumonia based on the same symptoms and recovered after antibiotic treatment. Chest CT scans on admission showed a consolidation and thickened pleura in the right lower lobe. Bronchoalveolar lavage fluids showed an alveolar hemorrhage. Lung biopsy specimens showed thickened pulmonary arteries and fibrotic nonspecific interstitial pneumonia (NSIP). Three years later, she was admitted with fever and pain of the left arm and aortitis syndrome was diagnosed. In this case of NSIP pattern associated with aortitis syndrome we speculate that repeated pulmonary infarction and alveolar hemorrhages caused the NSIP pattern.

A 37-year-old woman admitted elsewhere for a high fever, dry cough, stridor, and dyspnea was found in chest radiography and computed tomography on admission to have a thickened bronchial wall with centrilobular nodules in both lower lobes and skipped consolidations in the lower and middle lobe of the right lung. She had been diagnosed with mycoplasmal pneumonia because of high Mycoplasma pneumoniae antibody titer, so clarithromycin (CAM) was administrated. She was referred to us due to hypoxia with obstructive impairment in the pulmonary function test. Ventilation/perfusion radioisotope in the lung scan indicated heterogeneous distribution without mismatch, suggesting bronchiolitis obliterans due to M. pneumoniae pneumonia, so steroids were started. Five weeks of steroid administration ameliorated clinical symptoms, hypoxia, and abnormal shadows, but obstructive impairment diod not disappear completely. Early administration of steroid with antibiotics is required for bronchiolitis obliterans caused by M. pneumoniae. We review cases of mycoplasmal bronchiolitis reported in Japan.

A 15-year-old girl was admitted to our hospital because of polydipsia, polyuria, bilateral hilar lymphadenopathy and uveitis. A diagnosis of sarcoidosis with central diabetes insipidus was made by radiological, serological, bronchoalveolar lavage examinations, fluid restriction test and vasopression test. Prednisolone therapy improved all of her clinical findings except diabetes insipidus. So she had to continue intranasal 1-desamino-8-arginine vasopressin (DDAVP) therapy. In addition, we reviewed the clinical features of 27 patients of sarcoidosis with diabetes insipidus reported in Japan. They included 12 patients in young men and 21 patients having uveitis. These patients showed low frequency of lung complications in comparison with sarcoidosis without diabetes insipidus. Steroid therapy improved the symptoms of diabetes insipidus in only 3 patients, and all these 3 patients started steroid therapy within 1 month after the onset. Therefore we think that early diagnosis and treatment are important. Though central neurosarcoidosis was generally considered to have poor prognosis, there were only 3 patients who had recurrence by steroid tapering.

A 76-year-old man admitted for general malaise with fever was found in clinical examination on admission to have eosinophilic pleural effusion, peripheral eosinophilia, and a slightly elevated inflammatory reaction. Immunological examination, including microplate ELISA, showed a high titer of specific antibody against Toxocara canis in both the serum and pleural effusion. We started treatment using albendazole, and found inflammatory findings and serum IgE were ameliorated. Parasitic disease is an important consideration in the differential diagnosis of eosinophilic pleural effusion, and serology is useful in screening for this.

SELAPINA is generic product of PL granule which is one of the most common forms of combination remedies for the common cold in Japan, and includes acetaminophen. We report a case of SELAPINA-induced pneumonia successfully treated with glucocorticoid pulse therapy followed by orally administered prednisolone. A 68-year-old woman, who had been treated for rheumatoid arthiritis with pulmonary involvement, took SELAPINA with an antibiotic for 6 days because of her cold symptoms. She then suffered a high fever, cough, dyspnea, vomiting and diarrhea. Chest radiograph and high-resolution computed tomography (HRCT) scan revealed diffuse interstitial shadows. SELAPINA-induced pneumonia was diagnosed because the blastoid transformation test using her peripheral blood lymphocytes was positive on stimulation with SELAPINA, but negative for other medicines.

A 27-year old man who had developed uveitis, swelling of the right parotid gland, right facial nerve paralysis and fever, was admitted to our hospital. A chest X-ray film showed bilateral hilar lymphadenopathy. Serum levels of angiotensin-converting enzyme and lysozyme were elevated. Histological findings of transbronchial lung biopsy specimens showed non-caseous epithelioid cell granulomas. Therefore, sarcoidosis was diagnosed. This case also fulfilled the criteria for Heerfordt's syndrome. Adiministration of prednisolone (PSL) initially improved the patient's symptoms, but rapid tapering of PSL worsened his symptoms. Thus, administration of high-dose PSL for a long time was required. He also showed elevated levels of TNF alpha in serum.

We report here 3 cases of chronic bird fancier's lung diagnosed immunologically using antibodies to pigeon dropping extract. None of the patients were bird fanciers but had indirect exposure to birds in their living environment, and had been using feather-filled duvets or pillows for a long time. Two of 3 cases were positive for environmental provocation tests and 2 cases had pathological findings of hypersensitivity pneumonitis such as multinucleated giant cells and non-necrotizing epithelioid cell granulomas. One case was resistant to steroid therapy alone and was successfully treated by coadministration of prednisolone and cyclosporin A. Another case was treated by steroid alone but died of acute exacerbation of unknown cause. These cases suggest that not only feathers but two or more kinds of bird-related antigens were involved in the sensitization immunology and development of bird fancier's disease, and that clinicians should perform thorough history taking with environmental surveillance relevant to birds.

A 31-year-old woman was admitted due to swollen cervical lymph nodes and swollen tonsils. These did not respond to treatment by antibiotics, and histological findings of epithelioid cell granulomas were obtained by tonsillar biopsy. After corticosteroid therapy in the subcutaneous tissue of the upper arm 5 nodules were found discontinuously in a straight line. A biopsy of one of these nodules revealed non-caseous epithelioid cell granuloma with Langhans giant cells in the superficial lymph nodes. Her older brother was strongly suspected to have neurogenic sarcoidosis. Familial sarcoidosis was considered related to this case.

A 29-year-old woman was admitted to our hospital because of persistent breathlessness on exertion after the delivery of her second child. Although at the age of 26 she had been given a diagnosis of multiple pulmonary arteriovenous fistula (PAVF), treatment was not done because of the absence of symptoms. An intrauterine growth retardation (IUGR) due to hypoxemia occurred during the second pregnancy, and then she delivered a 1,283g baby by cesarean section in the 36th gestation week. Her symptoms and hypoxemia improved after transcatheter embolization. Hereditary hemorrhagic telangiectasia was diagnosed on the basis of recurrent epistaxis since her childhood, pulmonary and hepatic vascular abnormality (PAVF and hepatic arterioportal shunt) and telangiectasis of the buccal mucosa and tongue. We should consider an early treatment of PAVF for young female because pregnancy may induce increase of arteriovenous shunt, fatal hemoptysis, infertility, miscarriage and IUGR.

A 37-year-old-woman was admitted to our hospital because of chest bilateral reticular shadow with fever, cough, general malaise and exertional dyspnea in the summer. A diagnosis of summer-type hypersensitivity pneumonitis (SHP) was made by radiological, serological and histological examinations. Her 10-year-old daughter had chest reticular shadows and similar symptoms. These two patients were positive for serum anti-Trichosporon cutaneum (T. asahii, T. mucoides) antibodies and T. asahii was identified from cultured samples obtained from their house. They recovered spontaneously after hospitalization or isolation from the antigen. We reviewed the clinical features in sixteen families with familial SHP reported in Japan. Children aged under 15 years old accounted for 34% and there was no gender difference among patients. This finding differs from the conventionally defined features of patients with SHP. Measurements of serum KL-6, SP-D and SP-A seem to be useful for auxiliary diagnosis and monitoring the disease activity of SHP, especially in pediatric cases who cannot undergo invasive evaluation.

A 59-year-old woman was admitted because of general fatigue, cough and progressive dyspnea about 5 months after treatment with simvastatin for hyperlipidemia. A chest radiograph and computed tomography scans revealed ground glass and reticular opacities in the right middle and lower lung fields. The percentage of peripheral blood eosinophils was elevated. After simvastatin was discontinued and administration of prednisolone was started, eosinophilia and reticular shadows improved. Drug lymphocyte stimulation test (DLST) for simvastatin was positive, so we diagnosed drug induced eosinophilic pneumonia. Now hyperlipidemia is treated frequently with HMG-CoA reductase inhibitor, but there are few reports demonstrating lung injury by this drug. We should be aware of lung side effects of HMG-CoA reductase inhibitor.

A 56-year-old woman presented with complaints of general malaise and left chest pain. Chest radiography and CT scanning revealed multiple nodules and infiltrations in both lung fields. Her symptoms diminished and the extent of some of the lung shadows decreased spontaneously. However, since new shadows appeared later in other parts of the lung, she was admitted to our hospital on September 3. A transbronchial lung biopsy was not adequate for diagnosing a particular disease. But thoracoscopic lung biopsy specimens revealed necrosis with localized pleural fibrosis, and so a diagnosis of pulmonary infarction was made. The patient did not have any underlying disease or coagulation abnormalities, but Sjögren's syndrome and an antipsychotic agent were suspected to be background factors.

A 53-year-old woman visited our hospital in July 2002 with complaints of skin eruptions on the face and extremities, dry cough and dyspnea. A diagnosis of amyopathic dermatomyositis (ADM) was made on the basis of characteristic skin lesions and skin biopsy findings with slight muscle symptoms and mild elevation of muscle enzymes. Interstitial shadows were observed in both lower lung fields on chest radiographs, and thoracoscopic lung biopsy specimens revealed a diffuse alveolar damage (DAD) pattern. After induction of chemotherapy with prednisolone (50 mg/day) and cyclosporin A (150 mg/day), the respiratory symptoms and interstitial shadows were gradually reduced. Although it is known that interstitial pneumonia has an acute course and poor prognosis in ADM, the present case responded well to the chemotherapy with prednisolone and cyclosporin A.

A 34-year-old man was admitted to our hospital because of continuous shortness of breath and abnormal chest shadows. Bronchiectasis had been suspected because of abnormal chest shadows during childhood. However, a chest CT scan obtained on admission did not show any bronchiectatic changes, but marked dilated blood vessels and emphysematous changes in the bilateral lower lobes were seen. A pulmonary angiogram showed normal pulmonary arteries in the arterial phase and diffuse dilated veins in the venous phase. Although he has been suffering also from liver cirrhosis type B with portal hypertension, we could not find any association between the liver cirrhosis and the lung lesions. This is a very rare case in which there is a possibility of congenital or idiopathic dilatation of the pulmonary veins.